US20110305654A1 - Anhydrous petroleum jelly/elastomer-free depigmenting compositions comprising a solubilized phenolic compound - Google Patents

Anhydrous petroleum jelly/elastomer-free depigmenting compositions comprising a solubilized phenolic compound Download PDF

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US20110305654A1
US20110305654A1 US12/994,886 US99488609A US2011305654A1 US 20110305654 A1 US20110305654 A1 US 20110305654A1 US 99488609 A US99488609 A US 99488609A US 2011305654 A1 US2011305654 A1 US 2011305654A1
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composition
pharmaceutical composition
anhydrous pharmaceutical
oil
hydroquinone
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Claire Mallard
Karine NADAU-FOURCADE
Fabienne Louis
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Galderma Research and Development SNC
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Galderma Research and Development SNC
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Assigned to GALDERMA RESEACH & DEVELOPMENT reassignment GALDERMA RESEACH & DEVELOPMENT ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LOUIS, FABIENNE, NADAU-FOURCADE, KARINE, MALLARD, CLAIRE
Publication of US20110305654A1 publication Critical patent/US20110305654A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • the present invention relates to a novel cosmetic or pharmaceutical depigmenting composition in the form of an anhydrous ointment not containing any petroleum jelly and free of elastomer having a high molecular weight, especially for topical application, comprising as a pharmaceutical active agent a dissolved phenolic derivative.
  • phenolic derivatives and more particularly polyphenols
  • the therapeutic use of these agents results from the observation of cutaneous depigmentations in the case of operatives in the rubber industry, in which some of these products are used as antioxidants.
  • numerous studies have confirmed their efficacy, alone or combined with other depigmenting agents [Jorge L. Sanchez, M.D. and Miguel Vazquez, M.D. International Journal of Dermatology January-February 1982 Vol. 21, pp. 55-58]. They are thus found to be active agents that are virtually indispensable in the treatment of hyperpigmentation and are consequently present in many commercial products.
  • hydroquinone is the pharmaceutical active agents most commonly used.
  • Hydroquinone has been the subject of filing of various patent applications, and in particular U.S. Pat. No. 3,856,934 in which hydroquinone is in combination with retinoic acid and a corticoid as a depigmenting composition.
  • Rucinol or lucinol, or 4-butylresorcinol is also a phenolic-based pharmaceutical active agent, of polyphenol type, sold as an agent for lightening brown marks associated with pigmentation disorders (the product Iklen®).
  • Phenolic derivatives thus appear as virtually unavoidable active agents in the treatment of hyperpigmentation and are consequently present in many commercial products.
  • hydroquinone, rucinol or salts or derivatives thereof are dissolved in the aqueous phase of the preparation.
  • phenolic derivatives such as hydroquinone or rucinol are often exposed to heat during the phase of preparing the composition, especially in standard emulsions, and this phenomenon initiates and accelerates the browning.
  • the second drawback due to the presence of phenolic derivatives such as hydroquinone, alone or in combination with other active agents in the composition, is their strong irritant power.
  • hydroquinone at high concentration can give rise to post-inflammatory hypermelanosis and ochronosis phenomena.
  • Treatment with hydroquinone may be accompanied by irritation that may lead to a post-inflammatory hyperpigmentation.
  • the incidence of the irritation depends on the hydroquinone concentration. This irritation is relatively high for 10% concentrations and reduces greatly for preparations with a 5% dose, and is considered to be virtually nonexistent at a concentration of 2% [“Les agents chimiques dépigmentants (Depigmenting chemical agents)” JP. Ortonne Ann. Dermatol. Venerol. 1986, 113: 733-736].
  • the chosen galenical form may thus play a predominant role in minimizing these effects.
  • phenolic-based pharmaceutical active agents and in particular hydroquinone or rucinol should be formulated in solubilized form in an anhydrous formulation.
  • compositions currently available on the market, or as described in patent application US 2006/0 120 979 and allowing the formulation of water-sensitive active principles, while at the same time affording them good chemical stability are generally compositions of ointment type, formed mainly from petroleum jelly or, in more recent formulations, from a large proportion of elastomer.
  • elastomer in relatively large amounts makes it possible to give a certain amount of viscosity to anhydrous formulations (patent US 2006/0 120 979) without the drawbacks of petroleum jelly.
  • elastomer in the present invention, its use is unsatisfactory for the following reasons: the high proportion of elastomer present in these formulations specifically prevents the incorporation of sufficient amounts of oily and waxy compounds that have the advantage of giving the preparation the desired emollient properties.
  • One of the aims of the present invention is to propose an anhydrous pharmaceutical composition free of petroleum jelly and free of elastomer, intended for topical application, which has a viscosity equivalent to that of ointments containing petroleum jelly, which is easy to prepare, which affords good chemical stability to the active agent and in which certain volatile compounds may be used.
  • the composition according to the invention especially has these advantages by virtue of its preparation process.
  • a subject of the invention is thus also the particularly advantageously process for preparing such a composition, in which the step of incorporating the active agent is performed at room temperature.
  • the desired viscosity of the composition according to the invention is obtained especially by means of the choice of fatty substances used.
  • Another aim of the present invention is to propose an anhydrous pharmaceutical composition free of petroleum jelly and free of elastomer, intended for topical application, with prolonged stability, allowing optimized release of the active agents while at the same time being very well tolerated.
  • the present invention thus relates to a novel stable composition in the form of an anhydrous composition not containing any petroleum jelly and free of elastomer, especially for topical application, comprising a dissolved phenolic-based pharmaceutical active agent of polyphenol type.
  • the anhydrous composition according to the present invention also shows excellent stability and harmlessness.
  • the term “elastomer” means a polyorganosiloxane elastomer.
  • anhydrous composition means a composition comprising an amount of water of less than or equal to 5% by weight relative to the total weight of the composition.
  • the composition does not contain any water.
  • stable composition means a chemically and physically stable composition.
  • chemical stability especially means that no degradation of the active agent is observed over time and at temperatures of between 4 and 40° C.
  • physical stability especially means that the compositions do not show any drop in viscosity over time and at temperatures between 4 and 40° C.
  • the subject of the present invention is thus an anhydrous pharmaceutical composition, characterized in that it comprises:
  • the said composition not containing any petroleum jelly or any polyorganosiloxane elastomer.
  • anhydrous composition according to the invention may be in the various known galenical forms, which a person skilled in the art will adapt to the particular use of the composition.
  • compositions according to the invention are preferably formulated for topical application.
  • topical application means external application to the skin or mucous membranes.
  • compositions according to the invention may be in any galenical form normally used for topical application.
  • European pharmacopoeias Edition 6.3—in the chapter: Préparations semi-solides pour application cuta Amsterdam [Semi-solid preparations for cutaneous application] or as defined in the decision trees of the American Food and Drug Administration (FDA) (CDER Data Standards Manual Definitions for topical dosage Forms).
  • compositions according to the invention may thus be in liquid, semi-solid, pasty or solid form, and more particularly in the form of ointments, oily solutions, dispersions of the lotion type, which may be two-phase lotions, serum, anhydrous or lipophilic gels, powders, impregnated pads, syndets, wipes, sprays, mousses, sticks, shampoos, compresses, washing bases, emulsions of liquid or semi-liquid consistency of the oil-in-glycol or glycol-in-oil type, a microemulsion, semi-liquid or solid suspensions of the white or coloured cream type, multiple or inverse emulsions, gel or pomade, suspensions of microspheres or nanospheres or of lipid or polymeric vesicles, or microcapsules, microparticles or nanoparticles, or polymeric or gelled patches for controlled release.
  • the lotion type which may be two-phase lotions, serum, anhydrous or lipophilic gels, powders, impregna
  • the anhydrous composition according to the invention is preferably an ointment.
  • the term “ointment” means a composition especially as defined in the American or European Pharmacopoeias mentioned above.
  • the FDA thus defines an ointment as a semi-solid composition comprising, as vehicle, less than 20% water and volatile compounds and more than 50% hydrocarbons, waxes or polyol.
  • creams decision tree of the American Food and Drug Administration (FDA)
  • the American Pharmacopoeia defines an ointment as being a product whose base is a vehicle that may belong to the following four classes: hydrocarbon base or absorbent base or water-washable base or water-soluble base.
  • the ointment as defined in the American Pharmacopoeia is of hydrocarbon base type.
  • the European Pharmacopoeia defines an ointment as being a one-phase composition in which liquids or solids may be dispersed.
  • the ointment according to the invention is preferentially a composition that is thick at room temperature, which comprises between 80% and 98% by weight, relative to the total weight of the composition, of hydrophobic compounds other than petroleum jelly.
  • hydrophobic compounds other than petroleum jelly are chosen especially from liquid oils alone or as a mixture, the said oils possibly being hydrocarbons, esters, plant oils and/or silicone oils, which are volatile or non-volatile, which may be gelled with lipophilic compounds that are solid at room temperature such as waxes, butters or fatty acid esters.
  • a measurement of the flow threshold may be performed in order to characterize the finished product.
  • VT550 Haake rheometer with an SVDIN measuring spindle was used.
  • the rheograms are produced at 25° C. and an imposed speed of 0 to 100 s ⁇ 1 .
  • the viscosity values are given at shear values of 4 s ⁇ 1 , 20 s ⁇ 1 , 100 s ⁇ 1 ( ⁇ ).
  • the term “flow threshold” ( ⁇ 0 expressed in Pascals) means the force (minimum shear stress) required to overcome the cohesion forces of Van der Waals type and to bring about flow.
  • room temperature means a temperature of between 20 and 30° C.
  • the anhydrous nature of the ointment not containing any petroleum jelly or any elastomer according to the invention makes it possible to avoid instability of the phenolic derivative, in particular its oxidation in aqueous medium.
  • the use of antioxidants of sulfite type that are essential for the stabilization of hydroquinone in aqueous medium is thus no longer necessary. Consequently, in one preferred mode according to the invention, the composition does not contain any sulfites and contains an amount of antioxidants strictly less than 0.3% and preferentially less than 0.2% by weight relative to the total weight of the composition.
  • antioxidants that may be used according to the invention are preferably antioxidants such as vitamin E and derivatives thereof, for instance DL- ⁇ -tocopherol or tocopheryl acetate from Roche; vitamin C and derivatives thereof, for instance ascorbyl palmitate from Roche, and butylhydroxytoluene sold under the name Nipanox BHT by Clariant.
  • anhydrous ointment according to the invention comprises:
  • the anhydrous composition according to the invention contains substantially no petroleum jelly, i.e. comprises not more than 1% by weight of petroleum jelly relative to the total weight of the composition.
  • phenolic-based pharmaceutical active agent means, in a non-limiting manner, polyphenols and more particularly hydroquinone, 4-hydroxyanisole, hydroquinone monoethyl ether, hydroquinone monobenzyl ether and rucinol or lucinol and salts thereof.
  • rucinol salts especially means salts formed with a pharmaceutically acceptable base, especially a mineral base such as sodium hydroxide, potassium hydroxide and aqueous ammonia or an organic base such as lysine, arginine or N-methylglucamine, but also the salts formed with fatty amines such as dioctylamine, aminomethylpropanol and stearylamine.
  • a pharmaceutically acceptable base especially a mineral base such as sodium hydroxide, potassium hydroxide and aqueous ammonia or an organic base such as lysine, arginine or N-methylglucamine, but also the salts formed with fatty amines such as dioctylamine, aminomethylpropanol and stearylamine.
  • Hydroquinone or rucinol is preferably used.
  • the amount of pharmaceutical active agents of phenolic derivative type is from 0.01% to 10% by weight, preferably from 0.05% to 6% by weight and more particularly from 0.01% to 5% by weight relative to the total weight of the composition.
  • the composition according to the invention comprises glyceryl behenate, derivatives thereof or mixtures thereof.
  • glyceryl behenate derivatives especially but not exclusively means glyceryl monobehenate, glyceryl dibehenate and tribehenine.
  • the composition according to the invention especially comprises, preferably, a mixture of glyceryl dibehenate, tribehenine and glyceryl behenate. Such a mixture is especially sold under the name Compritol 888 by Gattefosse.
  • the term “glyceryl behenate” will be understood as meaning glyceryl behenate, derivatives thereof or mixtures thereof.
  • Glyceryl behenate is an oily-phase thickener.
  • the glyceryl behenate sets to a solid over time and allows the preparation of a hydrophobic composition whose final viscosity is obtained only after a certain time.
  • the constituents and the process are effectively chosen so as to give the composition fluidity at the end of immediate manufacture, facilitating the homogenization of the various constituents, but a desired final viscosity about 24 hours after manufacture.
  • the composition comprises from 1% to 40%, preferably between 5% and 30% and even more preferentially from 10% to 25% by weight of glyceryl behenate relative to the total weight of the composition.
  • composition according to the invention may also comprise at least one additional lipophilic gelling agent, also known as a lipophilic thickener.
  • additional lipophilic gelling agent or thickener affords greater physical stability to the composition, in particular when the composition is subjected to temperatures of accelerated stability conditions (ICH criteria) at about 40° C.
  • ICH criteria accelerated stability conditions
  • these compounds are used in the present invention as “viscosity modifiers”: in particular, by appropriately selecting them, they ensure the stability of the composition at 40° C. This thus affords the compositions obtained better stability.
  • additional lipophilic thickeners or gelling agents means compounds different from glyceryl behenate, chosen especially from waxes, hydrogenated oils and fatty acid esters.
  • wax generally means a lipophilic compound, which is solid at room temperature (25° C.), with a reversible solid/liquid change of state, which has a melting point of greater than or equal to 30° C., which may be up to 200° C. and especially up to 120° C.
  • a melting point of greater than or equal to 30° C.
  • hydrophilic oil means oils obtained by catalytic hydrogenation of animal or plant oils containing linear or branched C 8 -C 32 fatty chains.
  • hydrophilic oil isomerized jojoba oil such as partially hydrogenated trans-isomerized jojoba oil manufactured or sold by the company Desert Whale under the commercial reference Iso-Jojoba-50®, hydrogenated sunflower oil, the hydrogenated castor oil sold especially under the name Cutina HR by Cognis, hydrogenated coconut oil and hydrogenated lanolin oil; hydrogenated castor oil will preferably be used.
  • the composition comprises an overall amount of glyceryl behenate and optionally of additional lipophilic thickeners or gelling agents of between 1% and 40% and preferably between 5% and 35% by weight relative to the total weight of the composition.
  • the composition comprises from 10% to 25% by weight of glyceryl behenate and from 0 to 30% and preferably from 1% to 10% by weight of additional lipophilic thickener.
  • composition free of elastomer means an anhydrous composition comprising not more than 1% by weight of elastomer relative to the total weight of the composition.
  • the ointment according to the invention does not contain any elastomer.
  • elastomer means any polyorganosiloxane elastomer, namely any chemically crosslinked siloxane polymer that has viscoelastic properties.
  • the desired viscosity of the composition according to the invention is obtained with the aid especially of glyceryl behenate and of the choice of the other fatty substances used.
  • the absence of elastomer in the composition especially makes it possible to introduce more oily compounds, thus giving the composition the desired emollient properties.
  • the absence of elastomer may especially make it possible to obtain a more pronounced effect of the glyceryl behenate, namely fluidity of the composition at the end of manufacture and a final viscosity reached about 24 hours after manufacture.
  • the composition also comprises at least one solvent for the phenolic-based pharmaceutical active agent.
  • Solvents for the phenolic derivative are especially solvents of alcoholic or glycolic type.
  • solvents of alcoholic type according to the invention include linear or branched aliphatic alcohols, such as anhydrous or non-anhydrous ethanol, isopropanol and butanol.
  • the composition according to the invention preferentially contains ethanol.
  • solvents of glycolic type according to the invention examples include propylene glycol, ethylene glycol, 1,3-butylene glycol and dipropylene glycol.
  • the solvents for the phenolic derivative of alcoholic or glycolic type that are preferred according to the invention are especially ethanol and propylene glycol.
  • the solvent for the phenolic-based pharmaceutical active agent is ethanol.
  • the total amount of solvent is between 1% and 80% by weight, preferably between 5% and 50% and more particularly, between 10% and 30% by weight relative to the total weight of the composition.
  • fatty substances chosen from the following list:
  • the amount thereof is between 0.05% and 98% by weight and preferably between 1% and 80% by weight.
  • composition according to the invention may also comprise at least one surfactant and/or at least one binder.
  • the surfactants used are preferably nonionic surfactants, which are used for example, but not exclusively, to facilitate the incorporation of certain constituents such as glycols into the oily phase of the composition.
  • esters of glycerol and optionally of polyethylene glycol such as the mixture of glyceryl stearate and of PEG-100 stearate, sold under the name Arlacel 165 by Uniqema, the mixture of glyceryl stearate and of PEG-75 stearate sold under the name Gelot 64 by Gattefossé, the glyceryl stearate sold under the name Cutina GMSV by Cognis; emulsifying waxes, such as the self-emulsifying wax sold under the name Polawax NF by Croda or the PEG-8 beeswax sold under the name Apifil by Gattefossé; the polysorbate 80 sold under the name Tween 80 by Uniqema; castor oil and derivatives, for instance the polyoxyethylenated castor oil from BASF sold under the trade name Cremophor EL or the mixture
  • the amount of surfactants is between 1% and 20% by weight and preferably between 1% and 10% by weight.
  • the composition may optionally comprise at least one binder.
  • binders that may be used, mention may be made of the magnesium stearate sold by Brenntag, the corn starch sold by Roquette, the talc sold by WCD, the cholesterol sold by Croda or the silica sold by Degussa.
  • the binders may be used in an amount of between 1% and 30% by weight and preferably between 1% and 20% by weight.
  • composition according to the invention may also contain additives at between 0 and 20% and preferably between 0 and 10% by weight relative to the total weight of the composition, these being additives that a person skilled in the art will select as a function of the desired effect.
  • composition according to the invention comprises, on a weight basis relative to the total weight:
  • composition according to the invention comprises, on a weight basis relative to the total weight:
  • composition according to the invention comprises, on a weight basis relative to the total weight:
  • a subject of the invention is also the use of the composition thus obtained, as a medicament.
  • the composition may be used for preparing a medicament intended for treating and preventing hyperpigmentary disorders such as melasma, chloasma, lentigo, senile lentigo, vitiligo, freckles, post-inflammatory hyperpigmentations caused by abrasion, a burn, a scar, a dermatitis or a contact allergy; naevi, genetically determined hyper-pigmentations, hyperpigmentations of metabolic or medicinal origin, melanomas or any other hyperpigmentary lesions.
  • hyperpigmentary disorders such as melasma, chloasma, lentigo, senile lentigo, vitiligo, freckles, post-inflammatory hyperpigmentations caused by abrasion, a burn, a scar, a dermatitis or a contact allergy
  • naevi genetically determined hyper-pigmentations, hyperpigmentations of metabolic or medicinal origin, melanomas or any other hyperpig
  • a subject of the invention is also the use of the composition in the cosmetic field.
  • compositions according to the invention also find an application in the cosmetic field, in particular in protecting against the harmful effects of sunlight, for preventing and/or combating light-induced or chronological ageing of the skin and the integuments.
  • the invention also relates to a non-therapeutic cosmetic treatment process for beautifying the skin and/or for improving its surface appearance, characterized in that a composition comprising at least one depigmenting agent is applied to the skin and/or its integuments.
  • a subject of the present invention is also a process for preparing the compositions according to the invention.
  • Such a process especially makes it possible to maintain the compounds in fluid form at the end of manufacture.
  • One of the essential characteristics of the process for preparing the compositions according to the invention is the incorporation of the active phase at room temperature, i.e. the final step of mixing of the phases is performed at room temperature.
  • room temperature means a temperature of between 20 and 30° C.
  • the term “active phase” means a phase containing at least one active principle.
  • the term “non-active phase” means a phase formed from any ingredient other than the active principle.
  • the non-active phase is preferentially an oily phase containing at least the glyceryl behenate, preferably with another oily compound as described previously.
  • the process for manufacturing the composition according to the invention is performed according to Example 1, characterized in that the phases containing the pharmaceutical active agents are mixed together at room temperature.
  • compositions according to the invention without, however, limiting its scope.
  • the amounts of the constituents are expressed as weight percentages relative to the total weight of the composition.
  • the physical stability is measured by macroscopic and microscopic observation of the formulation at room temperature, at 4° C. and at 40° C. after 1 month, 2 months and optionally 3 months.
  • the macroscopic observation makes it possible to ensure the physical integrity of the products and the microscopic observation makes it possible to check that there is no recrystallization of the dissolved active agent.
  • the chemical stability is measured by assaying the active agents by external calibration on HPLC, and the results are expressed as a percentage of recovery relative to the theoretical titre.
  • phase B Active Phase
  • phase B Dissolve the phenolic-based pharmaceutical active agent in the appropriate solvent, add one (or more) antioxidant(s), if necessary, and stir until the active agent has dissolved (phase B).
  • Packaging is performed at the end of manufacture since the product does not yet have its final viscosity.
  • Phases INCI name Formulation % A Glyceryl behenate 16.00 A Hydrogenated castor oil 2.00 A Caprylic/capric triglycerides 49.85 A PEG-8 caprylic/capric 3.00 glycerides A PPG-15 stearyl ether 5.00 B Ethanol 100 20.00 B DL- ⁇ -tocopherol 0.05 B Ascorbyl palmitate 0.1 B Hydroquinone 4.00
  • Example 2 shows good colour stability (absence of oxidation) for at least 3 months at room temperature, 40° C. and 4° C.
  • Phases INCI name Formulation % A Glyceryl behenate 16.00 A Hydrogenated castor oil 2.00 A Caprylic/capric triglyceride 57.85 B Ethanol 100 20.00 B DL- ⁇ -tocopherol 0.05 B Ascorbyl palmitate 0.10 B Hydroquinone 4.00
  • Phases INCI name Formulation % A Glyceryl behenate 16.00 A Hydrogenated castor oil 2.00 A Caprylic/capric triglycerides 42.85 B PPG-15 stearyl ether 15.00 B Ethanol 100 20.00 B DL- ⁇ -tocopherol 0.05 B Ascorbyl palmitate 0.10 B Hydroquinone 4.00
  • Phases INCI name Formulation % A Glyceryl behenate 16.00 A Hydrogenated castor oil 2.00 A Caprylic/capric triglycerides 48.85 A PPG-15 stearyl ether 5.00 B Ethanol 100 20.00 B DL- ⁇ -tocopherol 0.05 B Ascorbyl palmitate 0.10 B Rucinol 5.00

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US12/994,886 2008-05-30 2009-06-02 Anhydrous petroleum jelly/elastomer-free depigmenting compositions comprising a solubilized phenolic compound Abandoned US20110305654A1 (en)

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FR0853571A FR2931662B1 (fr) 2008-05-30 2008-05-30 Nouvelles compositions depigmentantes sous forme d'une composition anhydre sans vaseline et sans elastomere comprenant un derive phenolique solubilise.
FR0853571 2008-05-30
PCT/FR2009/051037 WO2009156676A1 (fr) 2008-05-30 2009-06-02 Nouvelles compositions dépigmentantes sous forme d'une composition anhydre sans vaseline et sans élastomère comprenant un dérivé phénolique solubilisé

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US9801971B2 (en) 2009-10-09 2017-10-31 Beiersdorf Ag Transdermal therapeutic patches containing 4-N-butylresorcinol

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FR2946249B1 (fr) * 2009-06-05 2012-07-06 Galderma Res & Dev Compositions topiques depigmentantes, et leurs utilisations.
FR2946250A1 (fr) * 2009-06-05 2010-12-10 Galderma Res & Dev Compositions topiques depigmentantes, et leurs utilisations.
US8524211B1 (en) * 2012-05-22 2013-09-03 Conopco, Inc. Vegetable sourced petrolatum cosmetic

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US20070025937A1 (en) * 2005-07-29 2007-02-01 L'oreal S.A. Cosmetic compositions containing hydroquinone

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US4466955A (en) * 1982-06-09 1984-08-21 Germaine Monteil Cosmetiques Corporation Skin bleaching stick containing hydroquinone
US4678663A (en) * 1984-02-06 1987-07-07 Nuetrogena Corporation Hydroquinone composition having enhanced bio-availability and percutaneous adsorption
FR2598420B1 (fr) * 1986-05-06 1991-06-07 Oreal Nouveaux esters retinoiques d'antibiotiques, leur procede de preparation et compositions pharmaceutiques et cosmetiques les contenant
ATE132736T1 (de) * 1990-06-21 1996-01-15 Revlon Consumer Prod Corp Kosmetische zubereitungen
US5234682A (en) * 1990-06-21 1993-08-10 Revlon Consumer Products Corporation Cosmetic compositions
US6228894B1 (en) * 1998-04-17 2001-05-08 Enhanced Derm Technologies, Inc. Softgel-compatible composition containing retinol
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US6110449A (en) * 1999-06-14 2000-08-29 The Procter & Gamble Company Anhydrous antiperspirant cream compositions improved perfume longevity
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FR2885527B1 (fr) * 2005-05-16 2007-06-29 Galderma Res & Dev Composition pharmaceutique comprenant un onguent oleagineux et de la vitamine d ou ses derives a l'etat solubilise
FR2909284B1 (fr) * 2006-11-30 2012-09-21 Galderma Sa Nouvelles compositions sous forme d'onguent sans vaseline comprenant un derive de vitamine d et eventuellement un anti-inflammatoire steroidien
FR2915682B1 (fr) * 2007-05-04 2009-07-03 Galderma Res & Dev Compositions depigmentantes dermatologiques et cosmetiques, leurs procedes de preparation, et leurs utilisations

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
US9801971B2 (en) 2009-10-09 2017-10-31 Beiersdorf Ag Transdermal therapeutic patches containing 4-N-butylresorcinol

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AU2009264012A1 (en) 2009-12-30
RU2010154278A (ru) 2012-07-10
CN102046159A (zh) 2011-05-04
FR2931662B1 (fr) 2010-07-30
JP2011521934A (ja) 2011-07-28
KR20110015028A (ko) 2011-02-14
EP2293789A1 (fr) 2011-03-16
MX2010012752A (es) 2010-12-21
FR2931662A1 (fr) 2009-12-04
WO2009156676A1 (fr) 2009-12-30
BRPI0907664A2 (pt) 2015-07-21

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